High-quality multimodal MRI with simultaneous EEG using conductive ink and polymer-thick film nets.

Objective Combining magnetic resonance imaging (MRI) and electroencephalography (EEG) provides a powerful tool for investigating brain function at varying spatial and temporal scales. Simultaneous acquisition of both modalities can provide unique information that a single modality alone cannot reveal. However, current simultaneous EEG-fMRI studies are limited to a small set of MRI sequences due to the image quality and safety limitations of commercially available MR-conditional EEG nets. We tested whether the Inknet2, a high-resistance polymer thick film (PTF) based EEG net that uses conductive ink, could enable the acquisition of a variety of MR image modalities with minimal artifacts by reducing the RF-shielding caused by traditional MR-conditional nets. Approach We first performed simulations to model the effect of the EEG nets on the magnetic field and image quality. We then performed phantom scans to test image quality with a conventional copper EEG net, with the new Inknet2, and without any EEG net. Finally, we scanned five human subjects at 3 Tesla (3T) and three human subjects at 7 Tesla (7T) with and without the Inknet2 to assess structural and functional MRI image quality. Main results Across these simulations, phantom scans, and human studies, the Inknet2 induced fewer artifacts than the conventional net and produced image quality similar to scans with no net present. Significance Our results demonstrate that high-quality structural and functional multimodal imaging across a variety of MRI pulse sequences at both 3T and 7T is achievable with an EEG net made with conductive ink and polymer thick film technology. .

Real-world Decision-making Process for Stereotactic Body Radiotherapy Versus Minimally Invasive Surgery in Early-stage Lung Cancer Patients.

OBJECTIVE: To generate a prediction model for selection of treatment modality for early-stage non-small cell lung cancer (NSCLC). SUMMARY BACKGROUND DATA: Stereotactic body radiotherapy (SBRT) and minimally invasive surgery (MIS) are used in the local treatment of early-stage NSCLC. However, selection of patients for either SBRT or MIS remains challenging, due to the multitude of factors influencing the decision-making process. METHODS: We analyzed 1291 patients with clinical stage I NSCLC treated with intended MIS or SBRT from January 2020 to July 2023. A prediction model for selection for SBRT was created based on multivariable logistic regression analysis. The receiver operating characteristic curve analysis stratified the cohort into 3 treatment-related risk categories. Post-procedural outcomes, recurrence and overall survival (OS) were investigated to assess the performance of the model. RESULTS: In total, 1116 patients underwent MIS and 175 SBRT. The prediction model included age, performance status, previous pulmonary resection, MSK-Frailty score, FEV1 and DLCO, and demonstrated an area-under-the-curve of 0.908 (95%CI, 0.876-0.938). Based on the probability scores (n=1197), patients were stratified into a low-risk (MIS, n=970 and SBRT, n=28), intermediate-risk (MIS, n=96 and SBRT, n=53) and high-risk category (MIS, n=10 and SBRT, n=40). Treatment modality was not associated with OS (HR of SBRT, 1.67 [95%CI: 0.80-3.48]; P=0.20). CONCLUSION: Clinical expertise can be translated into a robust predictive model, guiding the selection of stage I NSCLC patients for MIS versus SBRT and effectively categorizing them into three distinct risk groups. Patients in the intermediate category could benefit most from multidisciplinary evaluation.

Native Valve Infective Endocarditis with Severe Regurgitation: What Matters Is Heart Failure.

Background/Objectives: Heart failure worsens the prognosis of patients with infective endocarditis (IE) and is mainly caused by severe valvular regurgitation. The aim of our investigation is to describe the clinical, epidemiological, microbiological, and echocardiographic characteristics of patients with native left-sided infective endocarditis (NLSIE) with severe valvular regurgitation; to describe the prognosis according to the therapeutic approach; and to determine the prognostic factors of in-hospital mortality. Methods: We prospectively recruited all episodes of possible or definite NLSIE diagnosed at three tertiary hospitals between 2005 and 2022. Patients were divided into two groups: patients with severe valvular regurgitation at the time of admission or during hospitalization and patients without severe valvular regurgitation. We analyzed up to 85 variables concerning epidemiological, clinical, analytical, microbiological, and echocardiographic data. Results: We recovered 874 patients with NLSIE, 564 (65%) of them with severe valvular regurgitation. There were no differences in mortality among patients with and without severe regurgitation (30.2% vs. 26.5%, p = 0.223). However, mortality increased when patients with severe regurgitation developed heart failure (33% vs. 11.4%, p < 0.001). Independent factors related to heart failure were age (OR 1.02 [1.01-1.034], p = 0.001), anemia (OR 1.2 [1.18-3.31], p = 0.01), atrial fibrillation (OR 2.3 [1.08-4.89], p = 0.03), S. viridans-related IE (OR 0.47 [0.3-0.73], p = 0.001), and mitroaortic severe regurgitation (OR 2.4 [1.15-5.02], p = 0.019). Conclusions: Severe valvular regurgitation is very frequent among patients with NLSIE, but it does not worsen the prognosis of patients unless complicated with heart failure.

Reference Sequence Browser: An R application with a user-friendly GUI to rapidly query sequence databases.

Land managers, researchers, and regulators increasingly utilize environmental DNA (eDNA) techniques to monitor species richness, presence, and absence. In order to properly develop a biological assay for eDNA metabarcoding or quantitative PCR, scientists must be able to find not only reference sequences (previously identified sequences in a genomics database) that match their target taxa but also reference sequences that match non-target taxa. Determining which taxa have publicly available sequences in a time-efficient and accurate manner currently requires computational skills to search, manipulate, and parse multiple unconnected DNA sequence databases. Our team iteratively designed a Graphic User Interface (GUI) Shiny application called the Reference Sequence Browser (RSB) that provides users efficient and intuitive access to multiple genetic databases regardless of computer programming expertise. The application returns the number of publicly accessible barcode markers per organism in the NCBI Nucleotide, BOLD, or CALeDNA CRUX Metabarcoding Reference Databases. Depending on the database, we offer various search filters such as min and max sequence length or country of origin. Users can then download the FASTA/GenBank files from the RSB web tool, view statistics about the data, and explore results to determine details about the availability or absence of reference sequences.

UNAM-HIMFG Bacterial Lysate Activates the Immune Response and Inhibits Colonization of Bladder of Balb/c Mice Infected with the Uropathogenic CFT073 Escherichia coli Strain.

Urinary tract infections (UTIs) represent a clinical and epidemiological problem of worldwide impact that affects the economy and the emotional state of the patient. Control of the condition is complicated due to multidrug resistance of pathogens associated with the disease. Considering the difficulty in carrying out effective treatment with antimicrobials, it is necessary to propose alternatives that improve the clinical status of the patients. With this purpose, in a previous study, the safety and immunostimulant capacity of a polyvalent lysate designated UNAM-HIMFG prepared with different bacteria isolated during a prospective study of chronic urinary tract infection (CUTI) was evaluated. In this work, using an animal model, results are presented on the immunostimulant and protective activity of the polyvalent UNAM-HIMFG lysate to define its potential use in the control and treatment of CUTI. Female Balb/c mice were infected through the urethra with Escherichia coli CFT073 (UPEC O6:K2:H1) strain; urine samples were collected before the infection and every week for up to 60 days. Once the animals were colonized, sublingual doses of UNAM-HIMFG lysate were administrated. The colonization of the bladder and kidneys was evaluated by culture, and their alterations were assessed using histopathological analysis. On the other hand, the immunostimulant activity of the compound was analyzed by qPCR of spleen mRNA. Uninfected animals receiving UNAM-HIMFG lysate and infected animals administered with the physiological saline solution were used as controls. During this study, the clinical status and evolution of the animals were evaluated. At ninety-six hours after infection, the presence of CFT073 was identified in the urine of infected animals, and then, sublingual administration of UNAM-HIMFG lysate was started every week for 60 days. The urine culture of mice treated with UNAM-HIMFG lysate showed the presence of bacteria for three weeks post-treatment; in contrast, in the untreated animals, positive cultures were observed until the 60th day of this study. The histological analysis of bladder samples from untreated animals showed the presence of chronic inflammation and bacteria in the submucosa, while tissues from mice treated with UNAM-HIMFG lysate did not show alterations. The same analysis of kidney samples of the two groups (treated and untreated) did not present alterations. Immunostimulant activity assays of UNAM-HIMFG lysate showed overexpression of TNF-α and IL-10. Results suggest that the lysate activates the expression of cytokines that inhibit the growth of inoculated bacteria and control the inflammation responsible for tissue damage. In conclusion, UNAM-HIMFG lysate is effective for the treatment and control of CUTIs without the use of antimicrobials.

Early Circulating Tumor DNA Shedding Kinetics for Prediction of Platinum Sensitivity in Patients With Small Cell Lung Cancer.

PURPOSE: Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine platinum sensitivity. MATERIALS AND METHODS: Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and on the first days of subsequent cycles with paired samples collected both before and again after infusions. Tumor-informed plasma analysis was carried out using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). The mean variant allele frequency (VAF) of all pretreatment mutations was tracked in subsequent blood draws and correlated with radiologic response. RESULTS: ctDNA kinetics were assessed in 122 samples from 21 patients. Pretreatment VAF did not differ significantly between patients who did and did not respond to chemotherapy (mean 22.5% v 4.6%, P = .17). A slight increase in ctDNA on cycle 1, day 1 immediately post-treatment was seen in six of the seven patients with available draws (fold change from baseline: 1.01-1.44), half of whom achieved a response. All patients who responded had a >2-fold decrease in mean VAF on cycle 2 day 1 (C2D1). Progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with a >2-fold decrease in mean VAF after one treatment cycle (6.8 v 2.6 months, log-rank P = .0004 and 21.7 v 6.4 months, log rank P = .04, respectively). CONCLUSION: A >2-fold decrease in ctDNA concentration was observed by C2D1 in all patients who were sensitive to platinum-based therapy and was associated with longer PFS and OS.

Pan-cancer genomic analysis reveals FOXA1 amplification is associated with adverse outcomes in non-small cell lung, prostate, and breast cancers.

INTRODUCTION: Alterations in forkhead box A1 (FOXA1), a pioneer transcription factor, are associated with poor prognosis in breast cancer (BC) and prostate cancer (PC). We characterized FOXA1 genomic alterations and their clinical impacts in a large pan-cancer cohort from the AACR GENIE database. METHODS: FOXA1 alterations were characterized across >87,000 samples from >30 cancer types for primary and metastatic tumors alongside patient characteristics and clinical outcomes. FOXA1 alterations were queried in the MSK-MET cohort (a GENIE subset), allowing definition of hazard ratios (HRs) and survival estimates based on Cox proportional hazard models. RESULTS: FOXA1 was altered in 1,869 samples (2.1%), with distinct patterns across different cancers: PC enriched with indel-inframe alterations, BC with missense mutations, and lung cancers with copy number (CN) amplifications.Of 74,715 samples with FOXA1 CN profiles, amplification was detected in 834 (1.1%). Amplification was most common in non-small cell lung cancer (NSCLC, 3% in primary; 6% in metastatic) and small cell lung cancer (4.1% primary; 3.5% metastatic), followed by BC (2% primary; 1.6% metastatic) and PC (2.2% primary; 1.6% metastatic).CN amplifications were associated with decreased overall survival in NSCLC (HR: 1.45, 95%CI: 1.06-1.99, p = .02), BC (HR: 3.04, 95%CI: 1.89-4.89, p = 4e-6), and PC (HR: 1.94, 95%CI: 1.03-3.68, p = .04). Amplifications were associated with wide-spread metastases in NSCLC, BC, and PC. CONCLUSIONS: FOXA1 demonstrates distinct alteration profiles across cancer sites. Our findings suggest an association between FOXA1 amplification and both enhanced metastatic potential and decreased survival, highlighting prognostic and therapeutic potential in breast cancer, prostate cancer, and NSCLC.

Optimal systemic treatment and real-world clinical application of ctDNA in patients with metastatic HER2-mutant lung cancer.

INTRODUCTION: No definitive answers currently exist regarding optimal first-line therapy for HER2-mutant NSCLC. Access to rapid tissue sequencing is a major barrier to precision drug development in the first-line setting. ctDNA analysis has the potential to overcome these obstacles and guide treatment. METHODS: We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing and received systemic therapy at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx LungTM assay. Primary endpoints were time to the next treatment (TTNT) and overall survival (OS). RESULTS: Sixty-three patients were included in the primary analysis. Chemoimmunotherapy (33/63, 52.4 %) was the predominant first-line treatment with a median TTNT of 5.1 months (95 %CI 4.1 - 6.1) whereas 55.0 % (22/40) of patients who received second-line T-DXd obtained a median TTNT of 9.2 m (95 % CI, 0-22.2). Plasma ctDNA was tested before first-line therapy in 40 patients with a median OS of 28.0 months (95 % CI 21-34), in whom 31 patients (78.0 %) had detectable ctDNA. HER2 mutations were detected on ctDNA with a median turnaround time of 13 days, occasionally co-occurred with EGFR and MET alterations and were tracked longitudinally correlating with treatment response. Patients with detectable baseline ctDNA had significantly shorter OS (hazard ratio (HR), 5.25; 95 % CI, 1.2-23.9; p = 0.019). CONCLUSION: Chemoimmunotherapy remains a major treatment option for metastatic HER2-mutant NSCLC. ctDNA can rapidly detect HER2 and co-mutations, and it has the potential to guide and monitor optimal first-line therapy. As a negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies.

Competing gauge fields and entropically driven spin liquid to spin liquid transition in non-Kramers pyrochlores.

Gauge theories are powerful theoretical physics tools that allow complex phenomena to be reduced to simple principles and are used in both high-energy and condensed matter physics. In the latter context, gauge theories are becoming increasingly popular for capturing the intricate spin correlations in spin liquids, exotic states of matter in which the dynamics of quantum spins never ceases, even at absolute zero temperature. We consider a spin system on a three-dimensional pyrochlore lattice where emergent gauge fields not only describe the spin liquid behavior at zero temperature but crucially determine the system's temperature evolution, with distinct gauge fields giving rise to different spin liquid phases in separate temperature regimes. Focusing first on classical spins, in an intermediate temperature regime, the system shows an unusual coexistence of emergent vector and tensor gauge fields where the former is known from classical spin ice systems while the latter has been associated with fractonic quasiparticles, a peculiar type of excitation with restricted mobility. Upon cooling, the system transitions into a low-temperature phase where an entropic selection mechanism depopulates the degrees of freedom associated with the tensor gauge field, rendering the system spin-ice-like. We further provide numerical evidence that in the corresponding quantum model, a spin liquid with coexisting vector and tensor gauge fields has a finite window of stability in the parameter space of spin interactions down to zero temperature. Finally, we discuss the relevance of our findings for non-Kramers magnetic pyrochlore materials.

Enhanced Energy Transfer in Cavity QED Based Phototransistors.

We leveraged strong light-matter coupling, a quantum process generating hybridized states, to prepare phototransistors using donor-acceptor pairs that transfer energy via Rabi oscillations. In a prototype experiment, we used a cyanine J-aggregate (TDBC; donor) and MoS2 monolayer (acceptor) in a field effect transistor cavity to study photoresponsivity. Energy migrates through the newly formed polaritonic ladder, with enhanced device efficiency when the cavity is resonant with donors. A theoretical model based on the time-dependent Schrödinger equation helped interpret results, with polaritonic states acting as a strong energy funnel to the MoS2 monolayer. These findings suggest novel applications of strong light-matter coupling in quantum materials.

Compositionally unique mitochondria in filopodia support cellular migration.

Local metabolic demand within cells varies widely and the extent to which individual mitochondria can be specialized to meet these functional needs is unclear. We examined the subcellular distribution of MICOS, a spatial and functional organizer of mitochondria, and discovered that it dynamically enriches at the tip of a minor population of mitochondria in the cell periphery that we term "METEORs". METEORs have a unique composition; MICOS enrichment sites are depleted of mtDNA and matrix proteins and contain high levels of the Ca2+ uniporter MCU, suggesting a functional specialization. METEORs are also enriched for the myosin MYO19, which promotes their trafficking to a small subset of filopodia. We identify a positive correlation between the length of filopodia and the presence of METEORs and show that elimination of mitochondria from filopodia impairs cellular motility. Our data reveal a novel type of mitochondrial heterogeneity and suggest compositionally specialized mitochondria support cell migration.

A supervised multiclass framework for mineral classification of Iberian beads.

Research on personal adornments depends on the reliable characterisation of materials to trace provenance and model complex social networks. However, many analytical techniques require the transfer of materials from the museum to the laboratory, involving high insurance costs and limiting the number of items that can be analysed, making the process of empirical data collection a complicated, expensive and time-consuming routine. In this study, we compiled the largest geochemical dataset of Iberian personal adornments (n = 1243 samples) by coupling X-ray fluorescence compositional data with their respective X-ray diffraction mineral labels. This allowed us to develop a machine learning-based framework for the prediction of bead-forming minerals by training and benchmarking 13 of the most widely used supervised algorithms. As a proof of concept, we developed a multiclass model and evaluated its performance on two assemblages from different Portuguese sites with current mineralogical characterisation: Cova das Lapas (n = 15 samples) and Gruta da Marmota (n = 10 samples). Our results showed that decisión-tres based classifiers outperformed other classification logics given the discriminative importance of some chemical elements in determining the mineral phase, which fits particularly well with the decision-making process of this type of model. The comparison of results between the different validation sets and the proof-of-concept has highlighted the risk of using synthetic data to handle imbalance and the main limitation of the framework: its restrictive class system. We conclude that the presented approach can successfully assist in the mineral classification workflow when specific analyses are not available, saving time and allowing a transparent and straightforward assessment of model predictions. Furthermore, we propose a workflow for the interpretation of predictions using the model outputs as compound responses enabling an uncertainty reduction approach currently used by our team. The Python-based framework is packaged in a public repository and includes all the necessary resources for its reusability without the need for any installation.

Escherichia coli Strains Isolated from American Bison (Bison bison) Showed Uncommon Virulent Gene Patterns and Antimicrobial Multi-Resistance.

E. coli is considered one of the most important zoonotic pathogens worldwide. Highly virulent and antimicrobial-resistant strains of E. coli have been reported in recent years, making it essential to understand their ecological origins. In this study, we analyzed the characteristics of E. coli strains present in the natural population of American bison (Bison bison) in Mexico. We sampled 123 individuals and determined the presence of E. coli using standard bacteriological methods. The isolated strains were characterized using molecular techniques based on PCR. To evaluate the diversity of E. coli strains in this population, we analyzed 108 suggestive colonies from each fecal sample. From a total of 13,284 suggestive colonies, we isolated 33 E. coli strains that contained at least one virulence gene. The virotypes of these strains were highly varied, including strains with atypical patterns or combinations compared to classical pathotypes, such as the presence of escV, eae, bfpB, and ial genes in E. coli strain LMA-26-6-6, or stx2, eae, and ial genes in E. coli strain LMA-16-1-32. Genotype analysis of these strains revealed a previously undescribed phylogenetic group. Serotyping of all strains showed that serogroups O26 and O22 were the most abundant. Interestingly, strains belonging to these groups exhibited different patterns of virulence genes. Finally, the isolated E. coli strains demonstrated broad resistance to antimicrobials, including various beta-lactam antibiotics.

An agent-based method to estimate 3D cell migration trajectories from 2D measurements: Quantifying and comparing T vs CAR-T 3D cell migration.

BACKGROUND AND OBJECTIVE: Immune cell migration is one of the key features that enable immune cells to find invading pathogens, control tissue damage, and eliminate primary developing tumors. Chimeric antigen receptor (CAR) T-cell therapy is a novel strategy in the battle against various cancers. It has been successful in treating hematological tumors, yet it still faces many challenges in the case of solid tumors. In this work, we evaluate the three-dimensional (3D) migration capacity of T and CAR-T cells within dense collagen-based hydrogels. Quantifying three-dimensional (3D) cell migration requires microscopy techniques that may not be readily accessible. Thus, we introduce a straightforward mathematical model designed to infer 3D trajectories of cells from two-dimensional (2D) cell trajectories. METHODS: We develop a 3D agent-based model (ABM) that simulates the temporal changes in the direction of migration with an inverse transform sampling method. Then, we propose an optimization procedure to accurately orient cell migration over time to reproduce cell migration from 2D experimental cell trajectories. With this model, we simulate cell migration assays of T and CAR-T cells in microfluidic devices conducted under hydrogels with different concentrations of type I collagen and validate our 3D cell migration predictions with light-sheet microscopy. RESULTS: Our findings indicate that CAR-T cell migration is more sensitive to collagen concentration increases than T cells, resulting in a more pronounced reduction in their invasiveness. Moreover, our computational model reveals significant differences in 3D movement patterns between T and CAR-T cells. T cells exhibit migratory behavior in 3D whereas that CAR-T cells predominantly move within the XY plane, with limited movement in the Z direction. However, upon the introduction of a CXCL12 chemical gradient, CAR-T cells present migration patterns that closely resemble those of T cells. CONCLUSIONS: This framework demonstrates that 2D projections of 3D trajectories may not accurately represent real migration patterns. Moreover, it offers a tool to estimate 3D migration patterns from 2D experimental data, which can be easily obtained with automatic quantification algorithms. This approach helps reduce the need for sophisticated and expensive microscopy equipment required in laboratories, as well as the computational burden involved in producing and analyzing 3D experimental data.

The AID2 system offers a potent tool for rapid, reversible, or sustained degradation of essential proteins in live mice.

Studying essential genes required for dynamic processes in live mice is challenging as genetic perturbations are irreversible and limited by slow protein depletion kinetics. The first-generation auxin-inducible-degron (AID) system is a powerful tool for analyzing inducible protein loss in cultured cells. However, auxin administration is toxic to mice, preventing its long-term use in animals. Here, we use an optimized second-generation AID system to achieve the conditional and reversible loss of the essential centrosomal protein CEP192 in live mice. We show that the auxin derivative 5-Ph-IAA is well tolerated over two weeks and drives near-complete CEP192-mAID degradation in less than one hour in vivo. Prolonged CEP192 loss led to cell division failure and cell death in proliferative tissues. Thus, the second-generation AID system is well suited for rapid and/or sustained protein depletion in live mice, offering a valuable new tool for interrogating protein function in vivo.

Radical cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal sarcomatosis: Results from a reference center and considerations based on current evidence.

INTRODUCTION: Peritoneal sarcomatosis is a rare disease, with multiple histological origins and poor overall prognosis. The option of radical cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The results of a surgical team experienced in these procedures are analyzed and discussed based on the available evidence. METHODS: Study on a prospective database of patients with peritoneal sarcomatosis who underwent CRS and HIPEC, from 2016 to 2022, in a national reference center for sarcomas and peritoneal oncological surgery, who met the established inclusion/exclusion criteria. RESULTS: 23 patients were included in the study, with a median age of 53 years (6-68). Recurrent/persistent clinical presentation predominated (78.3%). Visceral origin (including GIST and non-GIST peritoneal) accounted for 47.8% of patients, compared to 43.5% uterine and 8.7% retroperitoneal. The median PCI was 17 (3-36), with CC0 cytoreduction of 87%. Postoperative morbidity (Dindo Clavien III-IV) of 13%, with no postoperative mortality in the series. Overall survival and disease-free survival at 5 years were 64% and 34%, respectively. Histological grade was the most influential prognostic factor for survival. CONCLUSIONS: The results of the series, with low morbidity, support the benefit of radical peritoneal oncological surgery in patients with peritoneal sarcomatosis after adequate selection, as long as it is performed in high-volume centers, experienced surgeons and expert multidisciplinary teams. However, the role of HIPEC remains to be demonstrated and pending future studies.

Polyvalent Bacterial Lysate with Potential Use to Treatment and Control of Recurrent Urinary Tract Infections.

Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.

Early-life and chronic exposure to high-fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges.

Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.

Patient Safety and Satisfaction With Fully Remote Management of Radiation Oncology Care.

Importance: Patients of Memorial Sloan Kettering Cancer Center in New York, New York, are now offered a choice of either in-person or remote telehealth visits for radiation oncology care. However, safety and satisfaction among patients receiving treatment with fully remote physician management is unclear. Objective: To analyze patient safety and satisfaction, financial implications, and environmental consequences associated with fully remote management among a cohort of patients treated with radiotherapy. Design, Setting, and Participants: This single-institution retrospective cohort study was performed at Memorial Sloan Kettering Cancer Center, with patients treated with radiation who opted for fully remote management between October 1, 2020, and October 31, 2022. Data on patient safety events were prospectively collected with an in-house quality improvement reporting system. Patient satisfaction surveys were distributed electronically before, during, and after treatment. Patient transportation costs and environmental consequences were estimated based on differences in travel distance. Data analysis was performed from March 14 through September 19, 2023. Exposure: Radiotherapy with fully remote physician management. Main Outcomes and Measures: Satisfaction rates among patients opting for fully remote management were analyzed via surveys administered electronically after visits with clinicians. Patient safety events, defined as staff-reported actual events and near misses that had the potential to affect patient care, were reviewed. Rates and types of safety events were analyzed and compared with patients treated by onsite clinicians. Distances between patient home zip codes and treatment site locations were compared with estimated cost savings and decreased emissions. Results: This study included 2817 patients who received radiation oncology care with fully remote physician management. The median age of patients was 65 (range, 9-99) years, and more than half were men (1467 [52.1%]). Of the 764 safety events reported, 763 (99.9%) did not reach patients or caused no harm to patients. Nearly all survey respondents (451 [97.6%]) rated patient satisfaction as good to very good across all domains. For treatment with fully remote physician management, out-of-pocket cost savings totaled $612 912.71 ($466.45 per patient) and decreased carbon dioxide emissions by 174 metric tons. Conclusions and Relevance: In this study, radiation oncology care provided by fully remote clinicians was safe and feasible, with no serious patient events. High patient satisfaction, substantial cost savings, and decreased environmental consequences were observed. These findings support the continuation of a fully remote management option for select patients in the post-COVID-19 era.

Insurance Denials and Patient Treatment in a Large Academic Radiation Oncology Center.

Importance: Insurance barriers to cancer care can cause significant patient and clinician burden. Objective: To investigate the association of insurance denial with changes in technique, dose, and time to delivery of radiation oncology treatment. Design, Setting, and Participants: In this single-institution cohort analysis, data were collected from patients with payer-denied authorization for radiation therapy (RT) from November 1, 2021, to December 8, 2022. Data were analyzed from December 15, 2022, to December 31, 2023. Exposure: Insurance denial for RT. Main Outcomes and Measures: Association of these denials with changes in RT technique, dose, and time to treatment delivery was assessed using χ2 tests. Results: A total of 206 cases (118 women [57.3%]; median age, 58 [range, 26-91] years) were identified. Most insurers (199 [96.6%]) were commercial payers, while 7 (3.4%) were Medicare or Medicare Advantage. One hundred sixty-one patients (78.2%) were younger than 65 years. Of 206 cases, 127 (61.7%) were ultimately authorized without any change to the requested RT technique or prescription dose; 56 (27.2%) were authorized after modification to RT technique and/or prescription dose required by the payer. Of 21 cases with required prescription dose change, the median decrease in dose was 24.0 (range, 2.3-51.0) Gy. Of 202 cases (98.1%) with RT delivered, 72 (34.9%) were delayed for a mean (SD) of 7.8 (9.1) days and median of 5 (range, 1-49) days. Four cases (1.9%) ultimately did not receive any authorization, with 3 (1.5%) not undergoing RT, and 1 (0.5%) seeking treatment at another institution. Conclusions and Relevance: In this cohort study of patients with payer-denied cases, most insurance denials in radiation oncology were ultimately approved on appeal; however, RT technique and/or effectiveness may be compromised by payer-mandated changes. Further investigation and action to recognize the time and financial burdens on clinicians and clinical effects on patients caused by insurance denials of RT is needed.